Raymond S. Lance

Pathologic Variables and Recurrence Rates As Related to Obesity and Race in Men With Prostate Cancer Undergoing Radical Prostatectomy

PURPOSE To determine if obesity is associated with higher prostate specific antigen recurrence rates after radical prostatectomy (RP), and to explore racial differences in body mass index (BMI) as a potential explanation for the disparity in outcome between black and white men. PATIENTS AND METHODS A retrospective, multi-institutional pooled analysis of 3,162 men undergoing RP was conducted at nine US military medical centers between 1987 and 2002. Patients were initially categorized as obese (BMI > or = 30 kg/m(2)), overweight (BMI 25 to 30 kg/m(2)), or normal (BMI < or = 25 kg/m(2)). For analysis, normal and overweight groups were combined (BMI < 30 kg/m(2)) and compared with the obese group (BMI > or = 30 kg/m(2)) with regard to biochemical recurrence (prostate-specific antigen > or = 0.2 ng/mL) after RP. RESULTS Of 3,162 patients, 600 (19.0%) were obese and 2,562 (81%) were not obese. BMI was an independent predictor of higher Gleason grade cancer (P <.001) and was associated with a higher risk of biochemical recurrence (P =.027). Blacks had higher BMI (P <.001) and higher recurrence rates (P =.003) than whites. Both BMI (P =.028) and black race (P =.002) predicted higher prostate specific antigen recurrence rates. In multivariate analysis of race, BMI, and pathologic factors, black race (P =.021) remained a significant independent predictor of recurrence. CONCLUSION Obesity is associated with higher grade cancer and higher recurrence rates after RP. Black men have higher recurrence rates and greater BMI than white men. These findings support the hypothesis that obesity is associated with progression of latent to clinically significant prostate cancer (PC) and suggest that BMI may account, in part, for the racial variability in PC risk.

Limited value of bone scintigraphy and computed tomography in assessing biochemical failure after radical prostatectomy.

OBJECTIVES To define the utility of bone scan and computed tomography (CT) in the evaluation of patients with biochemical recurrence after radical prostatectomy. METHODS A retrospective analysis of the Center for Prostate Disease Research database was undertaken to identify patients who underwent radical prostatectomy between 1989 and 1998. Patients who developed biochemical recurrence (two prostate-specific antigen [PSA] levels greater than 0.2 ng/mL) and underwent either bone scan or CT within 3 years of this recurrence were selected for analysis. The preoperative clinical parameters, pathologic findings, serum PSA levels, follow-up data, and radiographic results were reviewed. RESULTS One hundred thirty-two patients with biochemical recurrence and a bone scan or CT scan were identified. Of the 127 bone scans, 12 (9.4%) were positive. The patients with true-positive bone scans had an average PSA at the time of the bone scan of 61.3 +/- 71.2 ng/mL (range 1.3 to 123). Their PSA velocities, calculated from the PSA levels determined immediately before the radiographic studies, averaged 22.1 +/- 24.7 ng/mL/mo (range 0.14 to 60.0). Only 2 patients with a positive bone scan had a PSA velocity of less than 0.5 ng/mL/mo. Of the 86 CT scans, 12 (14.0%) were positive. On logistic regression analysis, PSA and PSA velocity predicted the bone scan result (P <0.001 each) and PSA velocity predicted the CT scan result (P = 0.047). CONCLUSIONS Patients with biochemical recurrence after radical prostatectomy have a low probability of a positive bone scan (9.4%) or a positive CT scan (14.0%) within 3 years of biochemical recurrence. Most patients with a positive bone scan have a high PSA level and a high PSA velocity (greater than 0.5 ng/mL/mo).

Relationship between obesity and race in predicting adverse pathologic variables in patients undergoing radical prostatectomy.

OBJECTIVES To determine whether obesity is associated with more advanced prostate cancer (PCa) in radical prostatectomy patients and to explore the ethnic variability in body mass index (BMI) as a potential explanation for racial differences in PCa risk. METHODS A multi-institutional retrospective analysis of the clinical and pathologic parameters was performed on data from 860 patients with PCa undergoing radical prostatectomy between 1992 and 1998. Patient height and weight was used to calculate the BMI, which categorized patients into obese (BMI 30 kg/m(2) or greater), overweight (BMI 25 to 30 kg/m(2)), and normal (BMI 25 kg/m(2) or less) groups. Age, serum prostate-specific antigen level, pathologic stage, and Gleason score for each group were compared. The distribution of the BMI in each of four ethnic groups was also determined. RESULTS Of 860 patients, 171 (20%) were obese, 425 (49%) overweight, and 264 (31%) normal. The obese patients presented at a younger mean age (62 years, P = 0.001), had higher mean Gleason scores (6.7, P = 0.002), had a higher likelihood of Gleason score 7 or greater cancer (71%, P = 0.003), and had a lower chance of organ-confined cancer (46%, P = 0.050). The BMI was highest in blacks, followed by whites and Asians, and blacks had significantly higher grade cancers (P = 0.045). In multiple logistic regression analysis of the BMI and race, only BMI remained an independent predictor of Gleason grade. CONCLUSIONS Obese patients with PCa present for radical prostatectomy at a younger age with higher grade and more pathologically advanced cancers. Blacks have higher grade cancers than other ethnic groups and, at the same time, have significantly higher BMIs. These findings suggest that obesity may in part account for the racial variability in PCa risk.

A comparison of radical retropubic with perineal prostatectomy for localized prostate cancer within the Uniformed Services Urology Research Group.

Objective To review and compare the outcome of patients undergoing radical retropubic prostatectomy (RRP) or radical perineal prostatectomy (RPP) for clinically localized prostate cancer.

Urinary TMPRSS2:ERG and PCA3 in an Active Surveillance Cohort: Results from a Baseline Analysis in the Canary Prostate Active Surveillance Study

Purpose: Active surveillance is used to manage low-risk prostate cancer. Both PCA3 and TMPRSS2:ERG are promising biomarkers that may be associated with aggressive disease. This study examines the correlation of these biomarkers with higher cancer volume and grade determined at the time of biopsy in an active surveillance cohort. Experimental Design: Urine was collected after digital rectal examination prospectively as part of the multi-institutional Canary Prostate Active Surveillance Study (PASS). PCA3 and TMPRSS2:ERG levels were analyzed in urine collected at study entry. Biomarker scores were correlated to clinical and pathologic variables. Results: In 387 men, both PCA3 and TMPRSS2:ERG scores were significantly associated with higher volume disease. For a negative repeat biopsy, and 1% to 10%, 11% to 33%, 34% or more positive cores, median PCA3, and TMPRSS2:ERG scores increased incrementally (P < 0.005). Both PCA3 and TMPRSS2:ERG scores were also significantly associated with the presence of high-grade disease. For a negative repeat biopsy, Gleason 6 and Gleason ≥7 cancers, the median PCA3, and TMPRSS2:ERG scores also increased incrementally (P = 0.02 and P = 0.001, respectively). Using the marker scores as continuous variables, the ORs for a biopsy in which cancer was detected versus a negative repeat biopsy (ref) on modeling was 1.41 (95% CI: 1.07–1.85), P = 0.01 for PCA3 and 1.28 (95% CI: 1.10–1.49), P = 0.001 for TMPRSS2:ERG. Conclusions: For men on active surveillance, both PCA3 and TMPRSS2:ERG seem to stratify the risk of having aggressive cancer as defined by tumor volume or Gleason score. Clin Cancer Res; 19(9); 2442–50. ©2013 AACR.

OUTCOMES OF VARICOCELE LIGATION DONE FOR PAIN

PURPOSE Surgical ligation is an option in the management of patients with painful varicocele. Little objective data exist addressing the effectiveness of this treatment. We reviewed records from 58 patients who underwent varicocele ligation at our institution from January 1985 to May 1996 to establish success of surgical ligation of the painful varicocele. MATERIALS AND METHODS ICD-9 billing codes were used to identify all patients who had undergone varicocele ligation for pain since 1985. We documented patient age, grade and location of varicocele, duration and quality of pain, response to conservative therapy and surgical approach to ligation. Telephone interviews and chart reviews were conducted to determine resolution of pain, complications of the procedure and if the patient would choose surgery again. RESULTS We obtained followup on 35 of the 58 painful varicocele patients (60%). Average patient age was 25.7 years (range 15 to 65). The varicocele was on the left side in 30 men and bilateral in 5. Of the patients 31 described the pain as a dull throbbing ache, 2 as sharp and 2 as a pulling sensation. Initial conservative therapy failed in all 35 men. Varicocele was grade III in 18 cases, grade II in 16 and grade I in 1. The inguinal or subinguinal approach was used in 24 patients, high ligation in 10 and laparoscopic repair in 1. In 30 patients there was (86%) complete resolution of pain postoperatively and 1 had partial resolution. Only 4 patients (11%) had persistent or worse symptoms. CONCLUSIONS This retrospective review supports the conclusion that varicocele ligation is an effective treatment for painful varicocele in properly selected patients.

Temporarily Deferred Therapy (watchful waiting) for Men Younger Than 70 Years and With Low-Risk Localized Prostate Cancer in the Prostate-Specific Antigen Era

Purpose: Watchful waiting (WW) is an acceptable strategy for managing prostate cancer (PC) in older men. Prostate-specific antigen (PSA) testing has resulted in a stage migration, with diagnoses made in younger men. An analysis of the Department of Defense Center for Prostate Disease Research Database was undertaken to document younger men with low- or intermediate-grade PC who initially chose WW. Patients and Methods: We identified men choosing WW who were diagnosed between January 1991 and January 2002, were 70 years or younger, had a Gleason score ≤ 6 with no Gleason pattern 4, had no more than three positive cores on biopsy, and whose clinical stage was ≤ T2 and PSA level was ≤ 20. We analyzed their likelihood of remaining on WW, the factors associated with secondary treatment, and the influence of comorbidities. Results: Three hundred thirteen men were identified. Median follow-up time was 3.8 years. Median age was65.4 years (range, 41 to 70 years). Ninety-eight patients remained on WW; 215 proceeded...

Using the percentage of biopsy cores positive for cancer, pretreatment PSA, and highest biopsy Gleason sum to predict pathologic stage after radical prostatectomy: the center for prostate disease research nomograms☆

OBJECTIVES To develop probability nomograms to predict pathologic outcome at the time of radical prostatectomy (RP) on the basis of established prognostic factors and prostate biopsy quantitative histology. METHODS Using information from the database of the Center for Prostate Disease Research (CPDR), univariate and multivariate analyses were performed on 1510 men who had undergone transrectal ultrasound and biopsy for diagnosis and had radical prostatectomy as primary therapy, with variables of age, race, clinical stage, pretreatment prostate-specific antigen (PSA), biopsy Gleason sum, and percentage of biopsy cores positive for cancer (total number of cores positive for cancer divided by the total number of cores obtained). The percentages of biopsy cores positive were grouped as less than 30%, 30% to 59%, and greater than or equal to 60%. The three most significant variables were used to develop probability nomograms for pathologic stage. RESULTS PSA, biopsy Gleason sum, and percentage of cores positive were the three most significant independent predictors of pathologic stage. The assigned percentage of biopsy core-positive subgroups along with pretreatment PSA and highest Gleason sum were used to develop probability nomograms for pathologic stage. CONCLUSIONS Pretreatment PSA, highest biopsy Gleason sum, and the percentage of cores positive for cancer are the most significant predictors for pathologic stage after radical prostatectomy. On the basis of these findings, CPDR probability nomograms were developed to predict pathologic outcome at the time of RP.

Quality of Life After Open or Robotic Prostatectomy, Cryoablation or Brachytherapy for Localized Prostate Cancer

PURPOSE Health related quality of life concerns factor prominently in prostate cancer management. We describe health related quality of life impact and recovery profiles of 4 commonly used operative treatments for localized prostate cancer. MATERIALS AND METHODS Beginning in February 2000 all patients treated with open radical prostatectomy, robot assisted laparoscopic prostatectomy, brachytherapy or cryotherapy were asked to complete the UCLA-PCI questionnaire before treatment, and at 3, 6, 12, 18, 24, 30 and 36 months after treatment. Outcomes were compared across treatment types with statistical analysis using univariate and multivariate models. RESULTS A total of 785 patients treated between February 2000 and December 2008 were included in the analysis with a mean followup of 24 months. All health related quality of life domains were adversely affected by all treatments and recovery profiles varied significantly by treatment type. Overall urinary function and bother outcomes scored significantly higher after brachytherapy and cryotherapy compared to open radical prostatectomy and robotic assisted laparoscopic radical prostatectomy. Brachytherapy and cryotherapy had a 3-fold higher rate of return to baseline urinary function compared to open radical prostatectomy and robotic assisted laparoscopic radical prostatectomy. Sexual function and bother scores were highest after brachytherapy, with a 5-fold higher rate of return to baseline function compared to cryotherapy, open radical prostatectomy and robotic assisted laparoscopic radical prostatectomy. All 4 treatments were associated with relatively transient and less pronounced impact on bowel function and bother. CONCLUSIONS In a study of sequential health related quality of life assessments brachytherapy and cryotherapy were associated with higher urinary function and bother scores compared to open radical prostatectomy and da Vinci prostatectomy. Brachytherapy was associated with higher sexual function and bother scores compared to open radical prostatectomy, robotic assisted laparoscopic radical prostatectomy and cryotherapy.

Glycomic characterization of prostate-specific antigen and prostatic acid phosphatase in prostate cancer and benign disease seminal plasma fluids.

Prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) are glycoproteins secreted by prostate epithelial cells, and have a long clinical history of use as serum biomarkers of prostate cancers. These two proteins are present at significantly higher concentrations in seminal plasma, making this proximal fluid of the prostate a good source for purifying enough protein for characterization of prostate disease associated changes in glycan structures. With the use of seminal fluid samples representative of normal control, benign prostatic disease and prostate cancers, PAP and PSA were enriched by thiophilic absorption chromatography. Released N-linked glycan constituents from both proteins were analyzed by a combination of normal phase HPLC and MALDI-TOF spectrometry. For PSA, 40 putative glycoforms were determined, and 21 glycoforms were determined for PAP. PAP glycans were further analyzed with a hybrid triple quadrupole/linear ion trap mass spectrometer to assign specific glycoform classes to each of the three N-linked sites. The glycans identified in these studies will allow for more defined targeting of prostate disease-specific changes for PAP, PSA and other secreted prostatic glycoproteins.